The goal of this project is to carry out a systematic genetic analysis in the zebrafish Danio rerio, to understand the biological effects of alcohol on cell signaling. Understanding the molecular mechanisms that mediate cellular responses to acute or chronic ethanol treatment is not only important for understanding the complex signal transduction pathways and their cross regulation inside cells, but is also critical for understanding alcoholism, alcohol abuse, and the medical complications of excessive drinking. Simple and robust assays have been developed in zebrafish to assess the effects of acute as well as chronic alcohol exposure on cell signaling. By using these simple and powerful assays, we have carried out a pilot mutagenesis screen and identified mutations that display abnormal responses to either acute or chronic treatment of ethanol. These molecular genetic analyses will provide fundamental insights into signal transduction mechanisms and its modulation by acute and chronic alcohol exposure. Future behavioral and pathophysiological analyses can be done using the isolated zebrafish mutants. Further, molecules identified in zebrafish will provide candidate genes for association study of human alcoholism and alcoholic medical disorders. [unreadable] [unreadable] [unreadable]